We are asking for support to continue our analysis of the electrophysiological and pharmacological properties of retinal ganglion cells. The long-term goal of this research is to determine how electrical signals in retinal ganglion cells are controlled before being sent to the brain. The proposed experiments will test mechanisms of ion channel regulation and action potential inhibition in retinal ganglion cells of adult goldfish. The specific aims of this work are: (1) to examine whether multiple gamma-aminobutyric acid receptors (termed GABAA and GABAB function independently of each other - i.e., whether each type of GABA receptor can inhibit ganglion cells, and whether activation of each type of GABA receptor influences function of the other. (2) to map receptors for acetylcholine (ACh) and GABA across ganglion cell dendrites and somata, and test whether ACh and GABA receptors function independently of each other. (3) to examine whether and how GTP-binding proteins, protein kinases, phosphodiesterases and intracellular messengers mediate or influence GABAA, GABAB, and ACh receptors and associated ion channels in retinal ganglion cells. (4) to assess the effect of intracellular Ca2+ levels on ion channels in ganglion cells, and characterize ion channels which establish intracellular Ca2+ levels. Ganglion cells will be identified by retrograde labeling or by morphological features, and studied with patch-clamp and immunocytochemistry in vitro in primary cell cultures, in situ in tangentially microdissected pieces of living retina, and in cryostat sections. Because the receptors and channels we propose to study exhibit basic similarities in all vertebrate classes, results of the proposed experiments are expected to apply to visual systems in general. Because inhibitory and excitatory synaptic input to retinal ganglion cells enables our eyes to encode size and motion of objects and edges, the work we propose here will contribute to a fuller understanding of critical visual processes.